Fibrinogen (Fg) and fibrin (Fb) are hydrolyzed by plasmin in pathological fibrinogenolysis and fibrinolysis. This project is concerned with the development of a radioimmunoassay which is capable of differentiating between Fg and Fb degradation products (FDP) in human plasma. Hyper- and hypocoagulable states will be evaluated through an RIA of FDP which will distinguish between a primary fibrinolytic state and a disseminated intravascular coagulation followed by secondary fibrinolysis, permitting effecting effective treatment of abnormal hemostatic conditions. Human Fg is proteolyzed by plasmin to fragments D and E which are separable by QAE-Sephadex chromatography. Soluble, noncross-linked Fb is similarly digested to Fb-D and Fb-E. Rabbit anti-D and E sera are absorbed by passage through immunosorbent columns coupled with whole Fg. The two main RIA procedures, (1) double antibody RIA and (2) solid-phase RIA, will be developed for FDP in plasma based on the neoantigenic expression of D and E, respectively. Attempts will be made to produce antibodies specific only to Fb-E fragment by using the principle of immunological tolerance. Tolerance will be induced in rabbits to Fg-E. Rabbits will be hyperimmunized with Fb-E in order to produce antibodies capable of detecting "hypercoagulable states". The FDP levels of patients within the broad categories of obstetrical complications and cardiovascular diseases will be assayed. BIBLIOGRAPHIC REFERENCES: Chi, D.S. and J.P. Chen (1975), Fibrinogen-fibrin degradation products: Hemagglutination inhibition immunoassay in plasma. Texas Rep. Biol. Med. 33, 493-508. Chi, D.S. and J.P. Chen (1976), Comparative sensitivity of two hemagglutination inhibition immunoassays for fibrinolytic degradation products in human serum. Thromb. Haemost. 35, 423-436.